RNA Interference Approach Is a Good Strategy against SARS-CoV-2.

COVID-19, caused by SARS-CoV-2, created a devastating outbreak worldwide and consequently became a global health concern. However, no verifiable, specifically targeted treatment has been devised for COVID-19. Several emerging vaccines have been used, but protection has not been satisfactory. The complex genetic composition and high mutation frequency of SARS-CoV-2 have caused an uncertain vaccine response. Small interfering RNA (siRNA)-based therapy is an efficient strategy to control various infectious diseases employing post-transcriptional gene silencing through the silencing of target complementary mRNA. Here, we designed two highly effective shRNAs targeting the conserved region of RNA-dependent RNA polymerase (RdRP) and spike proteins capable of significant SARS-CoV-2 replication suppression. The efficacy of this approach suggested that the rapid development of an shRNA-based therapeutic strategy might prove to be highly effective in treating COVID-19. However, it needs further clinical trials.

SARS-CoV-2 infection aggravates cigarette smoke-exposed cell damage in primary human airway epithelia.

BACKGROUND: The coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic with over 627 million cases and over 6.5 million deaths. It was reported that smoking-related chronic obstructive pulmonary disease (COPD) might be a crucial risk for COVID-19 patients to develop severe condition. As cigarette smoke (CS) is the major risk factor for COPD, we hypothesize that barrier dysfunction and an altered cytokine response in CS-exposed airway epithelial cells may contribute to increased SARS-CoV-2-induced immune response that may result in increased susceptibility to severe disease. The aim of this study was to evaluate the role of CS on SARS-CoV-2-induced immune and inflammatory responses, and epithelial barrier integrity leading to airway epithelial damage. METHODS: Primary human airway epithelial cells were differentiated under air-liquid interface culture. Cells were then exposed to cigarette smoke medium (CSM) before infection with SARS-CoV-2 isolated from a local patient. The infection susceptibility, morphology, and the expression of genes related to host immune response, airway inflammation and damages were evaluated. RESULTS: Cells pre-treated with CSM significantly caused higher replication of SARS-CoV-2 and more severe SARS-CoV-2-induced cellular morphological alteration. CSM exposure caused significant upregulation of long form angiotensin converting enzyme (ACE)2, a functional receptor for SARS-CoV-2 viral entry, transmembrane serine protease (TMPRSS)2 and TMPRSS4, which cleave the spike protein of SARS-CoV-2 to allow viral entry, leading to an aggravated immune response via inhibition of type I interferon pathway. In addition, CSM worsened SARS-CoV-2-induced airway epithelial cell damage, resulting in severe motile ciliary disorder, junctional disruption and mucus hypersecretion. CONCLUSION: Smoking led to dysregulation of host immune response and cell damage as seen in SARS-CoV-2-infected primary human airway epithelia. These findings may contribute to increased disease susceptibility with severe condition and provide a better understanding of the pathogenesis of SARS-CoV-2 infection in smokers.

A Dual Adjuvant System for Intranasal Boosting of Local and Systemic Immunity for Influenza Vaccination.

Systemically vaccinated individuals against COVID-19 and influenza may continue to support viral replication and shedding in the upper airways, contributing to the spread of infections. Thus, a vaccine regimen that enhances mucosal immunity in the respiratory mucosa is needed to prevent a pandemic. Intranasal/pulmonary (IN) vaccines can promote mucosal immunity by promoting IgA secretion at the infection site. Here, we demonstrate that an intramuscular (IM) priming-IN boosting regimen with an inactivated influenza A virus adjuvanted with the liposomal dual TLR4/7 adjuvant (Fos47) enhances systemic and local/mucosal immunity. The IN boosting with Fos47 (IN-Fos47) enhanced antigen-specific IgA secretion in the upper and lower respiratory tracts compared to the IM boosting with Fos47 (IM-Fos47). The secreted IgA induced by IN-Fos47 was also cross-reactive to multiple influenza virus strains. Antigen-specific tissue-resident memory T cells in the lung were increased after IN boosting with Fos47, indicating that IN-Fos47 established tissue-resident T cells. Furthermore, IN-Fos47 induced systemic cross-reactive IgG antibody titers comparable to those of IM-Fos47. Neither local nor systemic reactogenicity or adverse effects were observed after IN delivery of Fos47. Collectively, these results indicate that the IM/IN regimen with Fos47 is safe and provides both local and systemic anti-influenza immune responses.

News literacy, fake news recognition, and authentication behaviors after exposure to fake news on social media

The global problem of online disinformation has led scholars, educators, and other stakeholders in societies to emphasize the utility of news literacy to engender more critical news audiences. Using a survey among a representative online sample of citizens in Hong Kong (N = 1485), this study examined how dispositional news literacy was related to individuals’ ability to discern real and fake COVID-related news on social media and their news authentication behaviors. Results showed that higher news literacy was related to greater ability to discern the veracity of real and fake news headlines;greater likelihood of certain internal acts of authentication when exposed to fake news (e.g. assessing content characteristics of the message);and greater likelihood to search online to verify fake news. The findings demonstrated the normative benefits of high dispositional news literacy among the general populace that can attenuate the effects of online disinformation. [ FROM AUTHOR] Copyright of New Media & Society is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Replication of SARS-CoV-2 Omicron BA.2 variant in ex vivo cultures of the human upper and lower respiratory tract.

BACKGROUND: The Omicron BA.2 sublineage has replaced BA.1 worldwide and has comparable levels of immune evasion to BA.1. These observations suggest that the increased transmissibility of BA.2 cannot be explained by the antibody evasion. METHODS: Here, we characterized the replication competence and respiratory tissue tropism of three Omicron variants (BA.1, BA.1.1, BA.2), and compared these with the wild-type virus and Delta variant, in human nasal, bronchial and lung tissues cultured ex vivo. FINDINGS: BA.2 replicated more efficiently in nasal and bronchial tissues at 33°C than wild-type, Delta and BA.1. Both BA.2 and BA.1 had higher replication competence than wild-type and Delta viruses in bronchial tissues at 37°C. BA.1, BA.1.1 and BA.2 replicated at a lower level in lung parenchymal tissues compared to wild-type and Delta viruses. INTERPRETATION: Higher replication competence of Omicron BA.2 in the human upper airway at 33°C than BA.1 may be one of the reasons to explain the current advantage of BA.2 over BA.1. A lower replication level of the tested Omicron variants in human lung tissues is in line with the clinical manifestations of decreased disease severity of patients infected with the Omicron strains compared with other ancestral strains. FUNDING: This work was supported by US National Institute of Allergy and Infectious Diseases and the Theme-Based Research Scheme under University Grants Committee of Hong Kong Special Administrative Region, China.

Respiratory Rate Estimation Using U-Net-Based Cascaded Framework From Electrocardiogram and Seismocardiogram Signals.

OBJECTIVE: At-home monitoring of respiration is of critical urgency especially in the era of the global pandemic due to COVID-19. Electrocardiogram (ECG) and seismocardiogram (SCG) signals-measured in less cumbersome contact form factors than the conventional sealed mask that measures respiratory air flow-are promising solutions for respiratory monitoring. In particular, respiratory rates (RR) can be estimated from ECG-derived respiratory (EDR) and SCG-derived respiratory (SDR) signals. Yet, non-respiratory artifacts might still be present in these surrogates of respiratory signals, hindering the accuracy of the RRs estimated. METHODS: In this paper, we propose a novel U-Net-based cascaded framework to address this problem. The EDR and SDR signals were transformed to the spectro-temporal domain and subsequently denoised by a 2D U-Net to reduce the non-respiratory artifacts. MAJOR RESULTS: We have shown that the U-Net that fused an EDR input and an SDR input achieved a low mean absolute error of 0.82 breaths per minute (bpm) and a coefficient of determination (R2) of 0.89 using data collected from our chest-worn wearable patch. We also qualitatively provided insights on the complementariness between EDR and SDR signals and demonstrated the generalizability of the proposed framework. CONCLUSION: ECG and SCG collected from a chest-worn wearable patch can complement each other and yield reliable RR estimation using the proposed cascaded framework. SIGNIFICANCE: We anticipate that convenient and comfortable ECG and SCG measurement systems can be augmented with this framework to facilitate pervasive and accurate RR measurement.

Parental Knowledge, Attitude, and Practice on Tobacco Use, Smoking Cessation, and Children's Environmental Tobacco Smoke Exposure.

Background: Environmental tobacco smoke (ETS) exposure in children ranks one of the major public health problems in our time. Poor parental knowledge, attitude, and practice (KAP) on ETS often contribute to worse exposure of the kids. Thus, we aimed to document parental KAP regarding tobacco use, smoking cessation and children's ETS exposure, and to analyse how knowledge and attitude relate to practice. Methods: Self-administered KAP questionnaires were distributed to smoking parents recruited from the pediatric unit at the Prince of Wales Hospital, which provides pediatric service to a population of 1.2 million in Hong Kong. The 60-item questionnaire had a range of 0-38 for knowledge, 0-44 for attitude, and 0-40 for practice. Descriptive analyses were performed for KAP response, regression analyses were performed for the exploration of associations and identification of predictive indicators. Results: 145 smoking parents (mean age: 38.0 ± 6.7 yrs.; male: 85.5%) were included. Less than half (39.3%) of them reported a smoke-free policy at home. Among those parents who had private cars, less than half (45.2%) of them had smoke-free policy in their car that they never smoked in the car. Only 25.5% of the participants correctly answered ≥70% of the knowledge questions, and 11.8 % of the participants gave favorable responses to ≥70% of the attitude questions. The total knowledge and the total attitudes score were positively associated (r = 0.49, 95% CI: 0.35-0.79, p < 0.001), yet they were only modestly correlated with parental practice on children's ETS exposure. By multivariate regressions, potential predictive factors for more favorable parental KAP included higher household income, lower parental nicotine dependence level and breastfeeding practice. Conclusions: Parental KAP related to tobacco use and children's ETS exposure needs improvement to address the significant gap between recommended and actual practice. The weak association between knowledge and practice suggested that parental education alone is not adequate to combat ETS exposure in children.

Human liver organoid derived intra-hepatic bile duct cells support SARS-CoV-2 infection and replication.

Although the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by deranged parenchymal liver enzymes. Furthermore, the severity of liver damage has been shown to correlate with higher mortality. Overall, the mechanism behind the liver injury remains unclear. We showed in this study that intra-hepatic bile duct cells could be grown using a human liver organoid platform. The cholangiocytes were not only susceptible to SARS-CoV-2 infection, they also supported efficient viral replication. We also showed that SARS-CoV-2 replication was much higher than SARS-CoV. Our findings suggested direct cytopathic viral damage being a mechanism for SARS-CoV-2 liver injury.

COVID-19 and Construction: Impact Analysis on Construction Performance during Two Infection Waves in Victoria, Australia

This research outlines the fluctuation in confirmed active cases of coronavirus disease 2019 (COVID-19), as related to the changes in the Victoria state government’s rules and restrictions. Further, this study examines the impact of government restrictions on the performance of construction in Victoria, Australia. The data analyses in this paper identify the specific effects on industrial production, during the different lockdown stages, in three local construction companies. Companies were selected from different points along the supply chain. Company A is a supplier involved in the manufacturing of structural steel. Company B conducts logistics and procurement. Company C is a construction engineering business specializing in foundations. After reviewing relevant case studies and theories, data analyses were developed in collaboration with these companies. The results revealed that the impact of restrictions on the workers on individual construction projects was not significant. Stage 4 restrictions (Victoria’s highest lockdown level) significantly impacted overall income by limiting construction to only servicing essential infrastructure or essential businesses. The novel contribution of this study is the data analysis outcome for Victoria, where a high level of restrictions were experienced, such as curfew and enforced isolation at home, relative to other countries. In 2021 and 2022 (omicron variant dominated), Victoria was again at the brink of an infection wave, which showed a similar pattern to July 2020, and endured the world’s longest COVID-19 lockdown. The research findings contribute to the body of knowledge by providing empirical data analysis of each company, representing the economic impact of ordinary small and medium enterprises (SMEs) in construction.

Role of Epithelial-Endothelial Cell Interaction in the Pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health globally. Patients with severe COVID-19 disease progress to acute respiratory distress syndrome, with respiratory and multiple organ failure. It is believed that dysregulated production of proinflammatory cytokines and endothelial dysfunction contribute to the pathogenesis of severe diseases. However, the mechanisms of SARS-CoV-2 pathogenesis and the role of endothelial cells are poorly understood. METHODS: Well-differentiated human airway epithelial cells were used to explore cytokine and chemokine production after SARS-CoV-2 infection. We measured the susceptibility to infection, immune response, and expression of adhesion molecules in human pulmonary microvascular endothelial cells (HPMVECs) exposed to conditioned medium from infected epithelial cells. The effect of imatinib on HPMVECs exposed to conditioned medium was evaluated. RESULTS: We demonstrated the production of interleukin-6, interferon gamma-induced protein-10, and monocyte chemoattractant protein-1 from the infected human airway cells after infection with SARS-CoV-2. Although HPMVECs did not support productive replication of SARS-CoV-2, treatment of HPMVECs with conditioned medium collected from infected airway cells induced an upregulation of proinflammatory cytokines, chemokines, and vascular adhesion molecules. Imatinib inhibited the upregulation of these cytokines, chemokines, and adhesion molecules in HPMVECs treated with conditioned medium. CONCLUSIONS: We evaluated the role of endothelial cells in the development of clinical disease caused by SARS-CoV-2 and the importance of endothelial cell-epithelial cell interaction in the pathogenesis of human COVID-19 diseases.

SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo.

The emergence of SARS-CoV-2 variants of concern with progressively increased transmissibility between humans is a threat to global public health. The Omicron variant of SARS-CoV-2 also evades immunity from natural infection or vaccines1, but it is unclear whether its exceptional transmissibility is due to immune evasion or intrinsic virological properties. Here we compared the replication competence and cellular tropism of the wild-type virus and the D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) variants in ex vivo explant cultures of human bronchi and lungs. We also evaluated the dependence on TMPRSS2 and cathepsins for infection. We show that Omicron replicates faster than all other SARS-CoV-2 variants studied in the bronchi but less efficiently in the lung parenchyma. All variants of concern have similar cellular tropism compared to the wild type. Omicron is more dependent on cathepsins than the other variants of concern tested, suggesting that the Omicron variant enters cells through a different route compared with the other variants. The lower replication competence of Omicron in the human lungs may explain the reduced severity of Omicron that is now being reported in epidemiological studies, although determinants of severity are multifactorial. These findings provide important biological correlates to previous epidemiological observations.

Enabling Continuous Wearable Reflectance Pulse Oximetry at the Sternum.

In light of the recent Coronavirus disease (COVID-19) pandemic, peripheral oxygen saturation (SpO2) has shown to be amongst the vital signs most indicative of deterioration in persons with COVID-19. To allow for the continuous monitoring of SpO2, we attempted to demonstrate accurate SpO2 estimation using our custom chest-based wearable patch biosensor, capable of measuring electrocardiogram (ECG) and photoplethysmogram (PPG) signals with high fidelity. Through a breath-hold protocol, we collected physiological data with a wide dynamic range of SpO2 from 20 subjects. The ratio of ratios (R) used in pulse oximetry to estimate SpO2 was robustly extracted from the red and infrared PPG signals during the breath-hold segments using novel feature extraction and PPGgreen-based outlier rejection algorithms. Through subject independent training, we achieved a low root-mean-square error (RMSE) of 2.64 ± 1.14% and a Pearson correlation coefficient (PCC) of 0.89. With subject-specific calibration, we further reduced the RMSE to 2.27 ± 0.76% and increased the PCC to 0.91. In addition, we showed that calibration is more efficiently accomplished by standardizing and focusing on the duration of breath-hold rather than the resulting range in SpO2. The accurate SpO2 estimation provided by our custom biosensor and the algorithms provide research opportunities for a wide range of disease and wellness monitoring applications.

Risk Assessment for Highly Pathogenic Avian Influenza A(H5N6/H5N8) Clade 2.3.4.4 Viruses.

The numerous global outbreaks and continuous reassortments of highly pathogenic avian influenza (HPAI) A(H5N6/H5N8) clade 2.3.4.4 viruses in birds pose a major risk to the public health. We investigated the tropism and innate host responses of 5 recent HPAI A(H5N6/H5N8) avian isolates of clades 2.3.4.4b, e, and h in human airway organoids and primary human alveolar epithelial cells. The HPAI A(H5N6/H5N8) avian isolates replicated productively but with lower competence than the influenza A(H1N1)pdm09, HPAI A(H5N1), and HPAI A(H5N6) isolates from humans in both or either models. They showed differential cellular tropism in human airway organoids; some infected all 4 major epithelial cell types: ciliated cells, club cells, goblet cells, and basal cells. Our results suggest zoonotic potential but low transmissibility of the HPAI A(H5N6/H5N8) avian isolates among humans. These viruses induced low levels of proinflammatory cytokines/chemokines, which are unlikely to contribute to the pathogenesis of severe disease.

Virtual and Augmented Reality Direct Ophthalmoscopy Tool: A Comparison between Interactions Methods

Direct ophthalmoscopy (DO) is a medical procedure whereby a health professional, using a direct ophthalmoscope, examines the eye fundus. DO skills are in decline due to the use of interactive diagnostic equipment and insufficient practice with the direct ophthalmoscope. To address the loss of DO skills, physical and computer-based simulators have been developed to offer additional training. Among the computer-based simulations, virtual and augmented reality (VR and AR, respectively) allow simulated immersive and interactive scenarios with eye fundus conditions that are difficult to replicate in the classroom. VR and AR require employing 3D user interfaces (3DUIs) to perform the virtual eye examination. Using a combination of a between-subjects and within-subjects paradigm with two groups of five participants, this paper builds upon a previous preliminary usability study that compared the use of the HTC Vive controller, the Valve Index controller, and the Microsoft HoloLens 1 hand gesticulation interaction methods when performing a virtual direct ophthalmoscopy eye examination. The work described in this paper extends our prior work by considering the interactions with the Oculus Quest controller and Oculus Quest hand-tracking system to perform a virtual direct ophthalmoscopy eye examination while allowing us to compare these methods without our prior interaction techniques. Ultimately, this helps us develop a greater understanding of usability effects for virtual DO examinations and virtual reality in general. Although the number of participants was limited, n = 5 for Stage 1 (including the HTC Vive controller, the Valve Index controller, and the Microsoft HoloLens hand gesticulations), and n = 13 for Stage 2 (including the Oculus Quest controller and the Oculus Quest hand tracking), given the COVID-19 restrictions, our initial results comparing VR and AR 3D user interactions for direct ophthalmoscopy are consistent with our previous preliminary study where the physical controllers resulted in higher usability scores, while the Oculus Quest’s more accurate hand motion capture resulted in higher usability when compared to the Microsoft HoloLens hand gesticulation.

Pulmonary Vein Thrombosis in COVID-19.

Research on COVID-19, the cause of a rapidly worsening pandemic, has led to the observation of laboratory derangements such as a propensity towards a hypercoagulable state. However, there are currently no reports on the incidence of pulmonary venous thrombosis in the setting of COVID-19. We report a case in which follow-up chest CT scans revealed an expansile filling defect in a branch of the right inferior pulmonary vein, which is consistent with pulmonary venous thrombosis. Our objective was to provide insight into an uncommon sequela of COVID-19 and consequently garner increased clinical suspicion for pulmonary VTE during hospitalization.

Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir.

The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat to human health. Using a multidisciplinary approach, we identified and validated the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load by multiple orders of magnitude and synergizes with remdesivir in vitro. Mechanistically, we showed that simeprevir not only inhibits the main protease (Mpro) and unexpectedly the RNA-dependent RNA polymerase (RdRp) but also modulates host immune responses. Our results thus reveal the possible anti-SARS-CoV-2 mechanism of simeprevir and highlight the translational potential of optimizing simeprevir as a therapeutic agent for managing COVID-19 and future outbreaks of CoV.

Introduction of ORF3a-Q57H SARS-CoV-2 Variant Causing Fourth Epidemic Wave of COVID-19, Hong Kong, China.

We describe an introduction of clade GH severe acute respiratory syndrome coronavirus 2 causing a fourth wave of coronavirus disease in Hong Kong. The virus has an ORF3a-Q57H mutation, causing truncation of ORF3b. This virus evades induction of cytokine, chemokine, and interferon-stimulated gene expression in primary human respiratory cells.

Neuroimaging Findings of Hospitalized Covid-19 Patients: A Canadian Retrospective Observational Study.

PURPOSE: Coronavirus disease (COVID-19) has been associated with neurologic sequelae and neuroimaging abnormalities in several case series previously. In this study, the neuroimaging findings and clinical course of adult patients admitted with COVID-19 to a tertiary care hospital network in Canada were characterized. METHODS: This is a retrospective observational study conducted at a tertiary hospital network in Ontario, Canada. All adult patients with PCR-confirmed COVID-19 admitted from February 1, 2020 to July 22, 2020 who received neuroimaging related to their COVID-19 admission were included. CT and MR images were reviewed and categorized by fellowship-trained neuroradiologists. Demographic and clinical data were collected and correlated with imaging findings. RESULTS: We identified 422 patients admitted with COVID-19 during the study period. 103 (24.4%) met the inclusion criteria and were included: 30 ICU patients (29.1%) and 73 non-ICU patients (70.9%). A total of 198 neuroimaging studies were performed: 177 CTs and 21 MRIs. 17 out of 103 imaged patients (16.8%) had acute abnormalities on neuroimaging: 10 had macrohemorrhages (58.8%), 9 had acute ischemia (52.9%), 4 had SWI abnormalities (23.5%), and 1 had asymmetric sulcal effacement suggesting possible focal encephalitis (5.8%). ICU patients were more likely to have positive neuroimaging findings, more specifically acute ischemia and macrohemorrhages (P < 0.05). Macrohemorrhages were associated with increased mortality (P < 0.05). CONCLUSION: Macrohemorrhages, acute ischemia and SWI abnormalities were the main neuroimaging abnormalities in our cohort of hospitalized COVID-19 patients. Acute ischemia and hemorrhage were associated with worse clinical status.